Proteomics

Dataset Information

0

PPARs and c-Myc regulate metabolism of renal tubules


ABSTRACT: Different segments of renal tubules have distinct metabolic features and functions, and defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined. We demonstrated that the renal proximal tubule (PT) has high expression of fatty acid and lipid metabolism enzymes, which is transcriptionally upregulated by abundantly expressed peroxisome proliferator-activated receptor (PPAR)/γ to support active lipid metabolism. In contrast, the renal distal tubule (DT) has elevated glycolytic enzyme expression corresponding with high rates of glycolysis, and this increased expression is mediated by abundantly expressed c-Myc. In addition, Nrf2 upregulated glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-dependent malic enzyme 1 expression for NADPH production and antioxidation in the DT. Highly expressed PPARγ transcriptionally enhanced expression of the protease iRhom2 in the PT, which suppressed epidermal growth factor (EGF) expression and secretion, inhibiting EGF receptor activation-dependent glycolytic gene expression and maintaining the low level of glycolysis. PPARγ inhibition reduced iRhom2 expression and increased EGF and GLUT1 expression in the PT in mice, resulting in hypertrophy of renal tubules and inhibited kidney functions, which can be rescued by inhibition of glycolysis via treatment with 2-deoxy-D-glucose. These findings delineate instrumental molecular mechanisms underlying the active lipid metabolism and suppressed glycolysis in the PT and active glycolysis in the DT and reveal critical roles for PPARs and c-Myc in maintaining metabolic homeostasis in the kidney

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Kidney

DISEASE(S): Disease Free

SUBMITTER: Zhongshi Lyu  

LAB HEAD: Qin Zhou

PROVIDER: PXD007828 | Pride | 2018-11-15

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
MaxQuantOutput.tar.gz Other
TMT_F10_20140808.raw Raw
TMT_F1_20140808.raw Raw
TMT_F2_20140808.raw Raw
TMT_F3_20140808.raw Raw
Items per page:
1 - 5 of 11
altmetric image

Publications

PPARγ maintains the metabolic heterogeneity and homeostasis of renal tubules.

Lyu Zhongshi Z   Mao Zhaomin Z   Li Qianyin Q   Xia Yan Y   Liu Yamin Y   He Qingling Q   Wang Yingchun Y   Zhao Hui H   Lu Zhimin Z   Zhou Qin Q  

EBioMedicine 20181109


<h4>Background</h4>The renal tubules, which have distant metabolic features and functions in different segments, reabsorb >99% of approximately 180 l of water and 25,000 mmol of Na <sup>+</sup> daily. Defective metabolism in renal tubules is involved in the pathobiology of kidney diseases. However, the mechanisms underlying the metabolic regulation in renal tubules remain to be defined.<h4>Methods</h4>We quantitatively compared the proteomes of the isolated proximal tubules (PT) and distal tubul  ...[more]

Similar Datasets

2013-12-24 | E-GEOD-37133 | biostudies-arrayexpress
2022-02-16 | PXD021357 | Pride
2007-07-06 | E-GEOD-1690 | biostudies-arrayexpress
2010-11-01 | E-GEOD-23911 | biostudies-arrayexpress
2009-01-26 | E-GEOD-13668 | biostudies-arrayexpress
2011-02-01 | GSE23911 | GEO
2010-04-14 | E-MEXP-2136 | biostudies-arrayexpress
2015-11-25 | PXD002125 | Pride
2015-01-27 | E-GEOD-64959 | biostudies-arrayexpress
2019-12-17 | GSE142113 | GEO